viernes, 8 de julio de 2016

NCT02638909 Clinical Trial - National Cancer Institute || Ceritinib in Treating Patients with Activated Gastrointestinal Malignancies That Cannot Be Removed by Surgery

NCT02638909 Clinical Trial - National Cancer Institute

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Ceritinib in Treating Patients with Activated Gastrointestinal Malignancies That Cannot Be Removed by Surgery

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and over15-0802
NCI-2016-00335, NCT02638909

Trial Description

Summary

This phase II trial studies how well ceritinib works in treating patients with gastrointestinal malignancies that are activated by a mutation (any change in the deoxyribonucleic acid [DNA] sequence of a cell) and cannot be removed by surgery. Ceritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Further Study Information

PRIMARY OBJECTIVES:
I. To demonstrate the anti-tumor activity of ceritinib, as measured by clinical benefit rate (CBR) (as defined as the percentage of patients who have achieved complete response [CR], partial response [PR], and stable disease [SD] at 2 months per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) to ceritinib by investigator assessment.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of ceritinib.
II. To evaluate progression-free survival (PFS).
III. To evaluate overall survival (OS).
IV. To evaluate overall response rate (ORR).
OUTLINE:
Patients receive ceritinib orally (PO) once daily (QD). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 3 months.

Eligibility Criteria

Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of inoperable colorectal adenocarcinoma, pancreatic, hepatocellular, cholangiocarcinoma, small bowel, gastric or esophageal adenocarcinoma that carries an activated anaplastic lymphoma kinase (ALK) or reactive oxygen species (ROS)1 pathway
Patients must have received at least 1 line of cytotoxic chemotherapy
Patients must have archival tissue sample available, collected either at the time of diagnosis or any time since; if archival tissue is unavailable, patient must be eligible and willing to undergo a fresh tissue biopsy
Patients must have recovered from all toxicities related to prior anticancer therapies to grade =< 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.03) provided that concomitant medication is given prior to initiation of treatment with LDK378 [ceritinib], except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study; additionally, patients with any grade of alopecia are allowed on treatment
COHORT EXPANSION PHASE: Patient must have measurable lesions as defined by RECIST version 1.1 criteria
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
An absolute neutrophil count (ANC) >= 1,500/mcl
Platelets >= 75,000/mcl
Hemoglobin >= 8 g/dl
Serum creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
Calculated or measured creatinine clearance (CrCl) >= 30 mL/min
Serum total bilirubin < 1.5 x ULN
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x ULN; if liver involvement, AST and ALT =< 5.0 x ULN
Alkaline phosphatase =< 3.0 x ULN; if liver involvement, alkaline phosphatase =< 5.0 x ULN
Serum albumin >= 2.5 g/dl
Serum amylase =< 2 x ULN
Serum lipase =< 1 x ULN
Fasting plasma glucose =< 175 mg/dL (=< 9.8 mmol/L)
Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits at screening:
Potassium >= lower limit of normal (LLN)
Magnesium >= LLN
Phosphorus >= LLN
Total calcium (corrected for serum albumin) >= LLN
A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study (and for up to 12 weeks after the last dose of study drug) to minimize the risk of pregnancy; if the partner is pregnant or breastfeeding, the subject must use a condom; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy; WOCBP must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product; highly effective contraception methods include:
(a) Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
(b) Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
(c) Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be the sole partner for that subject
Combination of any two of the following (a+b or a+c or b+c)
Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception
Placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; in case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
Patients who have had chemotherapy or radiotherapy within 3 weeks (4 weeks for radiotherapy to the lung fields and 6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
Prior therapy with ceritinib or other ALK or ROS1 inhibitor agents
Patients who are currently receiving treatment with warfarin sodium (Coumadin®) or any other coumarin-derivative anti-coagulants
Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry to manage CNS symptoms
Impairment of GI function or GI disease that may significantly alter the absorption of ceritinib
History of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease
Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention)
Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 6 months prior to first study drug administration
Class II-IV New York Heart Association (NYHA) congestive heart failure
Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
Corrected QT (QTc) (Frederica) prolongation > 470 msec
Subjects with valvular heart disease CTCAE (version 4.0) grade 2
Known left ventricular ejection fraction (LVEF) < 50%
Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of participation:
Medication with a known risk of prolonging the QT interval or inducing torsades de pointes
Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A poly peptide 4/5 (CYP3A4/5)
Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, and/or cytochrome P450 family 2, subfamily C, polypeptide 9 (CYP2C9)
Therapeutic doses of warfarin sodium (Coumadin) or any other coumarin-derived anti-coagulant; anti-coagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban)
Unstable or increasing doses of corticosteroids
Enzyme-inducing anti-convulsive agents
Herbal supplements
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris (Canadian Cardiovascular Society grade II-IV despite medical therapy), cardiac arrhythmia, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements
Major surgical procedure, open biopsy, or significant traumatic injury less than 4 weeks or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 1 week from first dose of first study drug administration
Known inability to swallow up to five ceritinib (LDK378) capsules daily
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

University of Colorado Cancer Center - Anschutz Cancer Pavilion

  • National Cancer Institute
  • Novartis Pharmaceuticals Corporation
Christopher Hanyoung Lieu, Principal Investigator

Trial Sites

U.S.A.

Colorado
Aurora
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Christopher Hanyoung Lieu
Ph: 303-724-6390
Email: Christopher.Lieu@ucdenver.edu
Christopher Hanyoung Lieu
Principal Investigator
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.

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